MCID: SCC001
MIFTS: 52

Succinic Semialdehyde Dehydrogenase Deficiency malady

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Succinic Semialdehyde Dehydrogenase Deficiency

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Aliases & Descriptions for Succinic Semialdehyde Dehydrogenase Deficiency:

Name: Succinic Semialdehyde Dehydrogenase Deficiency 49 10 11 21 45 22 23 12 51 67 65
4-Hydroxybutyric Aciduria 10 21 45 22 23 51 67
Gamma-Hydroxybutyric Aciduria 10 21 22 23 51 67
Ssadh Deficiency 21 45 22 23 51 67
Succinate Semialdehyde Dehydrogenase Deficiency 67 24
Gaba Metabolic Defect 45 67
 
Succinic Semialdehyde Dehydrogenase 11
Gamma-Hydroxybutyric Acidemia 23
Gamma-Hydroxybutyricaciduria 45
4-Hydroxybutyricaciduria 23
Ssadhd 67
Ssadh 10

Characteristics:

Orphanet epidemiological data:

51
succinic semialdehyde dehydrogenase deficiency:
Inheritance: Autosomal recessive; Age of onset: Childhood

HPO:

61
succinic semialdehyde dehydrogenase deficiency:
Onset and clinical course: phenotypic variability, infantile onset
Inheritance: autosomal recessive inheritance


Classifications:



External Ids:

OMIM49 271980
Disease Ontology10 DOID:0060175
Orphanet51 22
ICD10 via Orphanet28 E72.8
MedGen34 C0268631
MeSH36 D000592
UMLS65 C0268631

Summaries for Succinic Semialdehyde Dehydrogenase Deficiency

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Genetics Home Reference:23 Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging. People with this condition can also have problems controlling eye movements. Less common features of succinic semialdehyde dehydrogenase deficiency include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.

MalaCards based summary: Succinic Semialdehyde Dehydrogenase Deficiency, also known as 4-hydroxybutyric aciduria, is related to surfactant metabolism dysfunction, pulmonary, 3 and hypotonia, and has symptoms including cognitive impairment, incoordination and muscular hypotonia. An important gene associated with Succinic Semialdehyde Dehydrogenase Deficiency is ALDH5A1 (Aldehyde Dehydrogenase 5 Family Member A1), and among its related pathways are Valproic Acid Pathway, Pharmacodynamics and Propanoate metabolism. Affiliated tissues include eye, brain and breast.

Disease Ontology:10 A gamma-amino butyric acid metabolism disorder that is characterized by a deficiency of succinic semialdehyde dehydrogenase resulting in elevated levels of gamma-hydroxybutyric acid.

NIH Rare Diseases:45 Succinic semialdehyde dehydrogenase (ssadh) deficiency is disorder that can cause a variety of neurological and neuromuscular problems. the signs and symptoms can be extremely variable among affected individuals and may include mild to severe intellectual disability; developmental delay (especially involving speech); hypotonia; difficulty coordinating movements (ataxia); and/or seizures. some affected individuals may also have decreased reflexes (hyporeflexia); nystagmus; hyperactivity; and/or behavioral problems. ssadh deficiency is caused by mutations in the aldh5a1 gene and is inherited in an autosomal recessive manner. management is generally symptomatic and typically focuses on treating seizures and neurobehavioral issues. last updated: 9/25/2013

UniProtKB/Swiss-Prot:67 Succinic semialdehyde dehydrogenase deficiency: A rare inborn error of 4-aminobutyric acid (GABA) metabolism, which leads to accumulation of 4-hydroxybutyric acid in physiologic fluids of patients. The disease is clinically characterized by developmental delay, hypotonia, mental retardation, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances.

OMIM:49 Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive neurologic disorder in which an... (271980) more...

Wikipedia:68 Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria or... more...

GeneReviews summary for NBK1195

Related Diseases for Succinic Semialdehyde Dehydrogenase Deficiency

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Graphical network of the top 20 diseases related to Succinic Semialdehyde Dehydrogenase Deficiency:



Diseases related to succinic semialdehyde dehydrogenase deficiency

Symptoms for Succinic Semialdehyde Dehydrogenase Deficiency

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Symptoms by clinical synopsis from OMIM:

271980

Clinical features from OMIM:

271980

Symptoms:

 51 (show all 7)
  • ataxia/incoordination/trouble of the equilibrium
  • hypotonia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • organic acid metabolism anomalies
  • autosomal recessive inheritance
  • seizures/epilepsy/absences/spasms/status epilepticus
  • psychic/behavioural troubles

HPO human phenotypes related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show all 26)
id Description Frequency HPO Source Accession
1 cognitive impairment hallmark (90%) HP:0100543
2 incoordination hallmark (90%) HP:0002311
3 muscular hypotonia hallmark (90%) HP:0001252
4 seizures typical (50%) HP:0001250
5 self-injurious behavior HP:0100716
6 hyperkinesis HP:0002487
7 eeg abnormality HP:0002353
8 status epilepticus HP:0002133
9 generalized myoclonic seizures HP:0002123
10 absence seizures HP:0002121
11 generalized tonic-clonic seizures HP:0002069
12 abnormality of metabolism/homeostasis HP:0001939
13 motor delay HP:0001270
14 hyporeflexia HP:0001265
15 global developmental delay HP:0001263
16 muscular hypotonia HP:0001252
17 ataxia HP:0001251
18 intellectual disability HP:0001249
19 hyperactivity HP:0000752
20 delayed speech and language development HP:0000750
21 anxiety HP:0000739
22 hallucinations HP:0000738
23 aggressive behavior HP:0000718
24 autism HP:0000717
25 psychosis HP:0000709
26 abnormality of eye movement HP:0000496

UMLS symptoms related to Succinic Semialdehyde Dehydrogenase Deficiency:


seizures, ataxia

Drugs & Therapeutics for Succinic Semialdehyde Dehydrogenase Deficiency

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Drugs for Succinic Semialdehyde Dehydrogenase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1Protective AgentsPhase 1, Phase 25651
2(3-aminopropyl)(n-butyl)phosphinic acidPhase 1, Phase 22
3Neurotransmitter AgentsPhase 1, Phase 214795
4Neuroprotective AgentsPhase 1, Phase 21376
5
Taurineexperimental, Nutraceutical26107-35-71123
Synonyms:
1-Aminoethane-2-sulfonate
1-Aminoethane-2-sulfonic acid
2-Aminoethanesulfonate
2-Aminoethanesulfonic acid
2-Aminoethylsulfonate
2-Aminoethylsulfonic acid
 
2-Sulfoethylamine
Aminoethylsulfonate
Aminoethylsulfonic acid
Taurine
b-Aminoethylsulfonate
b-Aminoethylsulfonic acid
beta-Aminoethylsulfonate
beta-Aminoethylsulfonic acid

Interventional clinical trials:

idNameStatusNCT IDPhase
1Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase DeficiencyRecruitingNCT02019667Phase 1, Phase 2
2PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase DeficiencyCompletedNCT00246870
3Brain Excitability in Patients With Succinic Semialdehyde Dehydrogenase DeficiencyCompletedNCT00132366
4Taurine Therapy for SSADH DeficiencyCompletedNCT01608178

Search NIH Clinical Center for Succinic Semialdehyde Dehydrogenase Deficiency

Genetic Tests for Succinic Semialdehyde Dehydrogenase Deficiency

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Genetic tests related to Succinic Semialdehyde Dehydrogenase Deficiency:

id Genetic test Affiliating Genes
1 Succinic Semialdehyde Dehydrogenase Deficiency22 ALDH5A1

Anatomical Context for Succinic Semialdehyde Dehydrogenase Deficiency

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MalaCards organs/tissues related to Succinic Semialdehyde Dehydrogenase Deficiency:

33
Eye, Brain, Breast, Placenta, Endothelial, Myeloid, Ovary

Animal Models for Succinic Semialdehyde Dehydrogenase Deficiency or affiliated genes

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Publications for Succinic Semialdehyde Dehydrogenase Deficiency

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Articles related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show top 50)    (show all 72)
idTitleAuthorsYear
1
A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression. (27117035)
2016
2
Eye Findings on Vigabatrin and Taurine Treatment in Two Patients with Succinic Semialdehyde Dehydrogenase Deficiency. (27104484)
2016
3
A case of acute onset succinic semialdehyde dehydrogenase deficiency: neuroimaging findings and literature review. (26499347)
2015
4
Succinic semialdehyde dehydrogenase deficiency of four Chinese patients and prenatal diagnosis for three fetuses. (26220405)
2015
5
Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood. (26268900)
2015
6
Succinic Semialdehyde Dehydrogenase Deficiency in a Chinese Boy: A Novel ALDH5A1 Mutation With Severe Phenotype. (25122112)
2014
7
A Novel Mutation of ALDH5A1 Gene Associated With Succinic Semialdehyde Dehydrogenase Deficiency. (25246302)
2014
8
Analysis of ALDH5A1 gene mutation in a Chinese Han family with succinic semialdehyde dehydrogenase deficiency]. (23926001)
2013
9
Therapeutic efficacy of magnesium valproate in succinic semialdehyde dehydrogenase deficiency. (23430529)
2013
10
Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (22739941)
2013
11
Succinic semialdehyde dehydrogenase deficiency: an inheritable neurometabolic disease]. (23516105)
2013
12
A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family. (23825041)
2013
13
Efficacy of vigabatrin intervention in a mild phenotypic expression of succinic semialdehyde dehydrogenase deficiency. (23430864)
2012
14
A novel ALDH5A1 mutation in a patient with succinic semialdehyde dehydrogenase deficiency. (22437753)
2012
15
Epilepsy in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (21664777)
2011
16
Neuropathology in succinic semialdehyde dehydrogenase deficiency. (20304328)
2010
17
Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency. (20445195)
2010
18
Sleep disorders in succinic semialdehyde dehydrogenase deficiency: a family report. (19896403)
2010
19
Head bobbing due to succinic semialdehyde dehydrogenase deficiency. (20548048)
2010
20
Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. (19667317)
2009
21
Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. (19172412)
2009
22
Circadian distribution of generalized tonic-clonic seizures associated with murine succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (18514581)
2008
23
'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up'. (18811705)
2008
24
Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency. (17438226)
2007
25
Clinical, cytogenetic and molecular characterization of a patient with combined succinic semialdehyde dehydrogenase deficiency and incomplete WAGR syndrome with obesity. (16545979)
2006
26
Succinic semialdehyde dehydrogenase deficiency: clinical, biochemical and molecular characterization of a new patient with severe phenotype and a novel mutation. (16542398)
2006
27
Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. (15582027)
2004
28
Liver-directed adenoviral gene transfer in murine succinate semialdehyde dehydrogenase deficiency. (15093183)
2004
29
Proton MR spectroscopy in succinic semialdehyde dehydrogenase deficiency. (15037717)
2004
30
Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency. (12829002)
2003
31
Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. (12743223)
2003
32
Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. (12891656)
2003
33
Succinic semialdehyde dehydrogenase deficiency in children and adults. (12891657)
2003
34
Rapid and sensitive detection of urinary 4-hydroxybutyric acid and its related compounds by gas chromatography-mass spectrometry in a patient with succinic semialdehyde dehydrogenase deficiency. (12127325)
2002
35
Selective involvement of the globus pallidus and dentate nucleus in succinic semialdehyde dehydrogenase deficiency. (12136353)
2002
36
Neuroleptic malignant syndrome in a patient with succinic semialdehyde dehydrogenase deficiency. (11819156)
2002
37
MRI findings in succinic semialdehyde dehydrogenase deficiency. (10774997)
2000
38
Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria). (9683595)
1998
39
4-Hydroxybutyric acid and the clinical phenotype of succinic semialdehyde dehydrogenase deficiency, an inborn error of GABA metabolism. (9553943)
1998
40
The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients. (9093300)
1997
41
Seizures in a boy with succinic semialdehyde dehydrogenase deficiency treated with vigabatrin (gamma-vinyl-GABA). (8803774)
1996
42
Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase deficiency. (7564230)
1995
43
Pre- and postnatal diagnosis of succinic semialdehyde dehydrogenase deficiency using enzyme and metabolite assays. (7707697)
1994
44
Prenatal detection of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) (8464836)
1993
45
Succinic Semialdehyde Dehydrogenase Deficiency (20301374)
1993
46
Succinic semialdehyde dehydrogenase deficiency associated with combined 4-hydroxybutyric and dicarboxylic acidurias: potential for clinical misdiagnosis based on urinary organic acid profiling. (2926573)
1989
47
Vigabatrin therapy in patient with succinic semialdehyde dehydrogenase deficiency. (2572834)
1989
48
Succinic semialdehyde dehydrogenase deficiency--a further case. (2433500)
1985
49
Succinic semialdehyde dehydrogenase deficiency. (6536727)
1984
50
Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism. (6627675)
1983

Variations for Succinic Semialdehyde Dehydrogenase Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

67 (show all 12)
id Symbol AA change Variation ID SNP ID
1ALDH5A1p.Cys93PheVAR_026199
2ALDH5A1p.Gly176ArgVAR_026200
3ALDH5A1p.Cys223TyrVAR_026201
4ALDH5A1p.Thr233MetVAR_026202
5ALDH5A1p.Asn255SerVAR_026203
6ALDH5A1p.Gly268GluVAR_026204
7ALDH5A1p.Asn335LysVAR_026205
8ALDH5A1p.Pro382LeuVAR_026206
9ALDH5A1p.Pro382GlnVAR_026207
10ALDH5A1p.Gly409AspVAR_026208
11ALDH5A1p.Val487GluVAR_026209
12ALDH5A1p.Gly533ArgVAR_026210

Clinvar genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

5
id Gene Variation Type Significance SNP ID Assembly Location
1ALDH5A1ALDH5A1, IVS9, G-T, +1single nucleotide variantPathogenic
2ALDH5A1ALDH5A1, IVS5, G-A, +1single nucleotide variantPathogenic
3ALDH5A1NM_170740.1(ALDH5A1): c.612G> A (p.Trp204Ter)single nucleotide variantPathogenicrs118203982GRCh37Chr 6, 24505099: 24505099
4ALDH5A1NM_170740.1(ALDH5A1): c.1273C> T (p.Arg425Ter)single nucleotide variantPathogenicrs118203983GRCh37Chr 6, 24528285: 24528285
5ALDH5A1NM_001080.3(ALDH5A1): c.1226G> A (p.Gly409Asp)single nucleotide variantPathogenicrs118203984GRCh37Chr 6, 24528277: 24528277
6ALDH5A1NG_008161.1: g.31299_33753del2455deletionPathogenicGRCh37Chr 6, 24521495: 24523949

Expression for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Search GEO for disease gene expression data for Succinic Semialdehyde Dehydrogenase Deficiency.

Pathways for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Pathways related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 19)
idSuper pathwaysScoreTop Affiliating Genes
1
Show member pathways
9.8ABAT, ALDH5A1
29.6ABAT, ALDH6A1
3
Show member pathways
9.3GAD1, GAD2
49.3GAD1, GAD2
59.3GAD1, GAD2
69.3GAD1, GAD2
7
Show member pathways
9.2ALDH1B1, ALDH3A2
89.2ALDH1B1, ALDH3A2
9
Show member pathways
9.2ALDH1B1, ALDH3A2
10
Show member pathways
9.0ABAT, GAD1, GAD2
11
Show member pathways
9.0ABAT, GAD1, GAD2
12
Show member pathways
8.8ALDH1B1, ALDH3A2, ALDH4A1
13
Show member pathways
8.7ABAT, ALDH5A1, GAD1, GAD2
14
Show member pathways
8.7ABAT, ALDH5A1, GAD1, GAD2
15
Show member pathways
8.7ABAT, ALDH5A1, GAD1, GAD2
16
Show member pathways
8.3ABAT, ALDH1B1, ALDH3A2, ALDH6A1
178.3ABAT, ALDH4A1, ALDH5A1, GAD1, GAD2
18
Show member pathways
7.2ABAT, ALDH1B1, ALDH3A2, ALDH6A1, GAD1, GAD2
19
Show member pathways
6.1ABAT, AKR7A2, ALDH1B1, ALDH3A2, ALDH4A1, ALDH5A1

GO Terms for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Cellular components related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1clathrin-sculpted gamma-aminobutyric acid transport vesicle membraneGO:00612029.3GAD1, GAD2

Biological processes related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1gamma-aminobutyric acid metabolic processGO:000944810.4ABAT, ALDH5A1
2neurotransmitter catabolic processGO:004213510.3ABAT, ALDH5A1
3neurotransmitter secretionGO:00072699.5ABAT, ALDH5A1, GAD1
4metabolic processGO:00081528.3ABAT, ALDH1B1, ALDH3A2, ALDH6A1

Sources for Succinic Semialdehyde Dehydrogenase Deficiency

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet